The Diabetes Control and Vascular Disease study seeks to determine the natural history of juvenile diabetes and the relation of diabetic glycemia and other determinants to the development of microvascular and macrovascular disease in a large homogeneous group of Type I diabetic patients. It is proposed to continue observations of this well-defined cohort to further characterize occurrences of diabetic complications in relation to their determinants. Our aims are to: 1) delineate and define the evolution of small vessel disease in the retina of these young- adult diabetics by serial ophthalmological examinations (clinical, fluorescein angiography, fundus photography, retinal blood flow measurement by the laser Doppler technique), 2) further refine our recently developed index of the rate of progression of early diabetic retinopathy and develop other empirical methods for hierarchical scoring of other phases of diabetic retinopathy, 3) relate the severity thus measured and its components to the characteristics of the patient and the disease (e.g. level of glycemia, muscle CBMT, hormonal, genetic factors), 4) explore the role of the genome in susceptibility to diabetes and its complications by examining, separately and jointly, the relation of extended major histocompatibility (MHC) haplotypes (chr. 6), haplotypes defined by restriction fragment length polymorphisms (RFLPs) of large DNA regions on the short arm of chr. 11, and RFLPs for human IGF-I, IGF-II and aldehyde reductases, and 5) complete the typing and establishment of permanent lymphoblastoid cell lines from every study participant and selected families.